Protection by Anti-β-Glucan Antibodies Is Associated with Restricted β-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence 英文参考文献.docVIP

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Protection by Anti-β-Glucan Antibodies Is Associated with Restricted β-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence 英文参考文献.doc

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Protection by Anti-β-Glucan Antibodies Is Associated with Restricted β-1,3 Glucan Binding Specificity and Inhibition of Fungal Growth and Adherence 英文参考文献

ProtectionbyAnti-b-GlucanAntibodiesIsAssociated withRestrictedb-1,3GlucanBindingSpecificityand InhibitionofFungalGrowthandAdherence AntonellaTorosantucci1,PaolaChiani1,CarlaBromuro1,FlaviaDeBernardis1,AngelinaS.Palma2 ,Yan Liu2,GiuseppinaMignogna3,BrunoMaras3,MarisaColone4,AnnaritaStringaro4,SilviaZamboni5 ,Ten Feizi2,AntonioCassone1* 1DepartmentofInfectious,ParasiticandImmune-mediatedDiseases,IstitutoSuperiorediSanita`, Rome,Italy,2GlycosciencesLaboratory,FacultyofMedicine,Imperial College London, London, United Kingdom, 3Department of Biochemical Sciences ‘A. Rossi Fanelli’, University of Rome ‘La Sapienza’, Rome, Italy, 4Departments of TechnologyandHealth,IstitutoSuperiorediSanita`, Rome,Italy,5DepartmentofTherapeuticResearchandMedicineEvaluation,IstitutoSuperiorediSanita`, Rome,Italy Abstract Anti-b-glucanantibodieselicitedbyalaminarin-conjugatevaccineconfercross-protectiontomicechallengedwithmajor fungal pathogens such as Candida albicans, Aspergillus fumigatus and Cryptococcus neoformans. To gain insights into protective b-glucan epitope(s) and protection mechanisms, we studied two anti-b-glucan monoclonal antibodies (mAb) with identical complementarity-determining regions but different isotypes (mAb 2G8, IgG2b and mAb 1E12, IgM). C. albicans,themostrelevantfungalpathogenforhumans,wasusedasamodel. BothmAbsboundtofungalcellsurface andtotheb1,3-b1,6glucanofthefungalcellwallskeleton,asshownbyimmunofluorescence,electron-microscopyand ELISA. They were also equally unable to opsonize fungal cells in a J774 macrophage phagocytosis and killing assay. However,onlytheIgG2bconferredsubstantialprotectionagainstmucosalandsystemiccandidiasisinpassivevaccination experiments in rodents. Competition ELISA and microarray analyses using sequence-defined glucan oligosaccharides showed that the protective IgG2b selectively bound to b1,3-linked (laminarin-like) glucose sequences whereas the non- protectiveIgMboundtob1,6-andb1,4-linkedglucosesequencesinadditio